The Scientist March 16, 1998 Biotech Firms On Quest For Apoptotic Therapies
Cell Pathways Inc., a privately owned <sic>molecular oncology firm based in Horsham, Pa., also seeks to interfere with the apoptotic pathway by using its lead compound, FGN-1 (Ixosulin). FGN-1 induces apoptosis in precancerous tumor cells while avoiding inf lammation. The compound is a metabolic byproduct of sulindac (Clinoril), an anti-inflammatory drug used to treat arthritis. Whitehouse Station, N.J.-based Merck & Co. Inc. manufactures sulindac.
Rifat Pamukcu, Cell Pathways' chief science officer, thought sulindac could also be an anti-cancer agent when he heard anecdotal reports that the compound seemed to suppress tumors in some patients. Epidemiological evidence lent credence to those reports. Studies showed that a sulfone metabolite of sulindac caused apoptosis independently of the mechanism that made the drug an effective anti-inflammatory agent (G.A. Piazza et al., Cancer Research, 57:2452-9, 1997).
Cell Pathways scientists then isolated the metabolite, turned it into an anti-cancer candidate, and began clinical trials, after noting that the drug resulted in low toxicity in animal models. Results from Phase III clinical trials look promising, attests Gary A. Piazza, Cell Pathways' senior director of cell biology, who notes that FGN-1 showed signs of causing precancerous polyp regression in earlier phases of the drug's testing.
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